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节肢动物毒液钾离子通道阻滞剂在涉及记忆获取和存储的中枢神经系统神经疾病中的治疗应用探索。

Towards therapeutic applications of arthropod venom k(+)-channel blockers in CNS neurologic diseases involving memory acquisition and storage.

作者信息

Gati Christiano D C, Mortari Márcia R, Schwartz Elisabeth F

机构信息

Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, 70910-900 Brasília, DF, Brazil.

出版信息

J Toxicol. 2012;2012:756358. doi: 10.1155/2012/756358. Epub 2012 Jun 4.

Abstract

Potassium channels are the most heterogeneous and widely distributed group of ion channels and play important functions in all cells, in both normal and pathological mechanisms, including learning and memory processes. Being fundamental for many diverse physiological processes, K(+)-channels are recognized as potential therapeutic targets in the treatment of several Central Nervous System (CNS) diseases, such as multiple sclerosis, Parkinson's and Alzheimer's diseases, schizophrenia, HIV-1-associated dementia, and epilepsy. Blockers of these channels are therefore potential candidates for the symptomatic treatment of these neuropathies, through their neurological effects. Venomous animals have evolved a wide set of toxins for prey capture and defense. These compounds, mainly peptides, act on various pharmacological targets, making them an innumerable source of ligands for answering experimental paradigms, as well as for therapeutic application. This paper provides an overview of CNS K(+)-channels involved in memory acquisition and storage and aims at evaluating the use of highly selective K(+)-channel blockers derived from arthropod venoms as potential therapeutic agents for CNS diseases involving learning and memory mechanisms.

摘要

钾通道是最具异质性且分布最广泛的离子通道群体,在所有细胞中发挥着重要作用,涵盖正常和病理机制,包括学习和记忆过程。作为多种不同生理过程的基础,钾通道被认为是治疗多种中枢神经系统(CNS)疾病的潜在治疗靶点,如多发性硬化症、帕金森病和阿尔茨海默病、精神分裂症、HIV - 1相关痴呆症以及癫痫。因此,这些通道的阻滞剂因其神经学效应,有可能成为这些神经病变对症治疗的候选药物。有毒动物已经进化出了多种毒素用于捕食和防御。这些化合物主要是肽,作用于各种药理学靶点,使其成为用于解答实验范式以及治疗应用的无数配体来源。本文概述了参与记忆获取和存储的中枢神经系统钾通道,并旨在评估源自节肢动物毒液的高度选择性钾通道阻滞剂作为涉及学习和记忆机制的中枢神经系统疾病潜在治疗药物的用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b78b/3373146/93772926e925/JT2012-756358.001.jpg

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